Field of the Invention
The invention relates generally to compositions and methods for treatment of epilepsy in an animal. Particularly, the present invention relates to the compositions and methods using medium chain triglycerides for the treatment of epilepsy. More particularly, the present invention relates to compositions and methods comprising medium chain triglycerides for enhancing the effect of antiepileptic drugs in animals.
Description of Related Art
Epilepsy is the most common chronic neurological disorder in humans and dogs with an estimated prevalence in dogs of 1-2% in a referral hospital population and 0.6% in first opinion practice. Higher prevalence's up to 18% have been reported in breed specific studies with up to 33% seen in certain families. Further, epilepsy has been associated with increased risk of premature and unexpected death, injuries, cognitive deterioration, neurobehavioral dysfunction and reduced quality of life. Despite on-going research in understanding the pathophysiological manifestation of seizures and epilepsy, the cellular mechanisms remain elusive. As a result, approaches towards epileptic therapy are usually directed towards the control of seizures, most commonly chronic administration of antiepileptic drugs (AEDs), rather than prevention of epileptogenesis or comorbidities. Some of the AEDs routinely used in canine epilepsy include phenobarbital (PB), potassium bromide (KBr), imepitoin, benzodiazepines, gabapentin and levetiracetam. Despite appropriate AED treatment, approximately one third of dogs and humans with idiopathic epilepsy continue to experience difficult to control seizures. Furthermore, AED related side effects such as ataxia, polyphagia, polyuria, polydipsia and incontinence also contribute to reduction in quality of life.
A myriad of anecdotal reports and published literature have suggested the importance of dietary manipulation in seizure management. In particular, the ketogenic diet (KD) has been proposed as an alternative treatment strategy for canine epilepsy. The classic KD consisting of high fat, low protein and low carbohydrate, typically with ratios of up to 4:1 fats to proteins and carbohydrates, was first introduced in the 1920s for use in human childhood epilepsy. The use of KD was initially suggested in order to mimic the metabolic state and biochemical changes associated with fasting, since fasting was proven to possess anticonvulsant properties. A randomized controlled trial in childhood epilepsy showed promising results with 38% and 9%, of the children on KD diet compared to control diet, having greater than 50% and 90% seizure reduction respectively. Current practice in human medicine to use the ‘classic’ KD diet as a prescription therapy relies on structuring the macronutrient ratio, whereby fat relative to a combined protein and carbohydrates is 4:1. Traditional ketogenic diet has been developed to control drug-resistant (refractory) epilepsy and typically contains 4:1 ratio of fat to protein plus carbohydrates by weight (Kossoff and Rho, ketogenic diets:evidence for short and long-term efficacy. Neurotherapeutics 6:406-414, 2009). In addition, a ketogenic diet with 60% of the calories from MCTs showed anti-epileptic benefits (Huttenlocher et al. Medium-chain triglycerides as a therapy for intractable childhood epilepsy. Neurology 21:1097-1103, 1971). However, such diets have been problematic due to palatability or restrictiveness of certain foods.
Though advances have been made, there remains a need to develop compositions and methods that can treat epilepsy in humans and other animals. Such therapies would be useful to improve the overall quality of life for all involved. For companion animals, these therapies would lead to improved owner satisfaction and would improve the owner-companion animal bond.